Objective To establish an acute exposure model of extreme plateau hypobaric hypoxia environment and explore transcriptomic changes related to learning and memory impairment in rats.  Methods Healthy male SD rats aged 6-weeks, 200-250 g, were selected and divided into control group and plateau group. The control group was treated with normal pressure and oxygen (19 rats), and the plateau group was placed in a hypobaric hypoxia chamber (19 rats) at a simulated altitude of 8000 meters and treated for 72 hours. Behavioral changes were detected with 16 animals from each group using contextual fear conditioning and Morris water maze (8 rats each). Three hippocampal tissues were extracted from each group for transcriptomic sequencing, and the molecular mechanism of learning and memory impairment induced by extreme plateau environment was analyzed by Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG) and gene set enrichment analysis(GSEA) enrichment.  Results The behavioral result  showed that compared with the control group, the fear memory and spatial learning memory abilities of rats in plateau group were decreased. GO and KEGG analyses showed that the extreme altitude environment reshaped the hippocampal microenvironment and affected the intercellular signal transmission, while GSEA analysis showed that the extreme altitude environment up-regulated the gene set related to the plasma membrane and extracellular matrix.  Conclusion The extreme plateau environment at an altitude of 8000 meters could affect the microenvironment of rat hippocampus, destroy intercellular connections and impair intercellular communication and then induce learning and memory impairment.